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TASK FORCE REPORT
ERS/ATS TECHNICAL STANDARDS
2017 ERS/ATS standards for single-breath

carbon monoxide uptake in the lung
Brian L. Graham1, Vito Brusasco2, Felip Burgos3, Brendan G. Cooper4,
Robert Jensen5, Adrian Kendrick6, Neil R. MacIntyre7,
Bruce R. Thompson8 and Jack Wanger9
Affiliations: 1Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan,
Saskatoon, SK, Canada. 2Dept of Internal Medicine, University of Genoa, Genoa, Italy. 3Respiratory Diagnostic
Center, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of
Barcelona, Barcelona, Spain. 4Lung Function and Sleep, Queen Elizabeth Hospital, University of Birmingham,
Birmingham, UK. 5Pulmonary Division, University of Utah, Salt Lake City, UT, USA. 6Dept of Respiratory
Medicine, Bristol Royal Infirmary, Bristol, UK. 7Pulmonary, Allergy and Critical Care Medicine, Duke University
Medical Center, Durham, NC, USA. 8Allergy, Immunology and Respiratory Medicine, The Alfred Hospital and
Monash University, Melbourne, Australia. 9Consultant, Rochester, MN, USA.
Correspondence: Brian L. Graham, Division of Respirology, Critical Care and Sleep Medicine, University of
Saskatchewan, Saskatoon, SK, Canada, S7N 0W8. E-mail: brian.graham@usask.ca
@ERSpublications
Updated technical standards for measuring DLCO (TLCO) including the use of rapid gas analyser
systems http://ow.ly/QUhv304PMsy
Cite this article as: Graham BL, Brusasco V, Burgos F, et al. 2017 ERS/ATS standards for single-breath
carbon monoxide uptake in the lung. Eur Respir J 2017; 49: 1600016 [https://doi.org/10.1183/
13993003.00016-2016].
ABSTRACT This document provides an update to the European Respiratory Society (ERS)/American
Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was
last updated in 2005. Although both DLCO (diffusing capacity) and TLCO (transfer factor) are valid terms
to describe the uptake of carbon monoxide in the lung, the term DLCO is used in this document. A joint
taskforce appointed by the ERS and ATS reviewed the recent literature on the measurement of DLCO and
surveyed the current technical capabilities of instrumentation being manufactured around the world. The
recommendations in this document represent the consensus of the taskforce members in regard to the
evidence available for various aspects of DLCO measurement. Furthermore, it reflects the expert opinion of
the taskforce members on areas in which peer-reviewed evidence was either not available or was
incomplete. The major changes in these technical standards relate to DLCO measurement with systems
using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most
common type of DLCO instrumentation being manufactured. Technical improvements and the increased
capability afforded by these new systems permit enhanced measurement of DLCO and the opportunity to
include other optional measures of lung function.
This article has supplementary material available from erj.ersjournals.com

Received: Jan 04 2016 | Accepted after revision: July 24 2016
This report was approved by the ATS Board of Directors in August 2016, and endorsed by the ERS Science Council and
Executive Committee in September 2016. An executive summary of these standards is available as https://doi.org/10.
1183/13993003.E0016-2016.
Support statement: This report was supported by the American Thoracic Society (grant: FY2015) and the European
Respiratory Society (grant: TF-2014-19). Funding information for this article has been deposited with the Open Funder
Registry.
Conflict of interest: None declared.
Copyright ©ERS 2017
https://doi.org/10.1183/13993003.00016-2016 Eur Respir J 2017; 49: 1600016

ERS/ATS TECHNICAL STANDARDS | B.L. GRAHAM ET AL.
Background
It has been over 100 years since Marie Krogh developed a method to measure the single-breath uptake of
carbon monoxide in the lungs [1]. Her experiment was designed to show that passive diffusion could explain
oxygen transfer from the alveolar gas to the pulmonary capillary blood, but the methodology became the
basis of the test, now in common use, which is called diffusing capacity in North America but is more
appropriately called transfer factor in Europe. The abbreviation for transfer factor or diffusing capacity of the
lung for carbon monoxide used in this document is DLCO, although TLCO is an equally valid term.
A standardised clinical method of determining the diffusing capacity of the lung for carbon monoxide was
described by OGILVIE et al. [2] in 1957 using a tracer gas to determine both the alveolar volume and the
alveolar concentration of carbon monoxide at the beginning of breath-holding. This method used the
collection of discrete exhaled gas samples from which gas concentrations were measured using gas
analysers that took up to several minutes to perform the measurements. In the remainder of this
document we will term these “classical” systems and calculations. The instrumentation for DLCO
measurement has advanced considerably since then, primarily through the use of rapidly responding gas
analyser (RGA) systems with gas analysers that have a 0–90% response time of ⩽150 ms. While RGAs are
capable of real-time, continuous gas analysis, most modern systems generally use this advanced
instrumentation only to simulate the classical collection of discrete samples of gas in a bag and discard
most of the sampled gas data. However, as discussed later, there are several aspects of DLCO measurement
that can be improved markedly using all of the data provided by this continuous measurement technology.
This document and the accompanying executive summary document [3] are an update of the 2005
American Thoracic Society (ATS) and European Respiratory Society (ERS) standards [4] which, in turn,
built upon previous standards [5, 6]. This update reflects the consensus opinions of both of these societies
and is designed to: 1) provide an update to the standards required for DLCO systems based on RGA
systems; and 2) provide new calculation standards that incorporate continuous gas analysis of the entire
exhaled sample. It is recognised that classical equipment will remain in use for some time. However, some
previously designed DLCO systems can be upgraded and re-engineered to meet these new RGA system
standards. It is expected that as new DLCO systems are designed and built, they will meet and, in many
cases, exceed these new standards. This document is meant to function as a stand-alone work but, for
certain issues, reference will be made to previous statements. The following recommendations will be
restricted to the single-breath technique of measuring the uptake of carbon monoxide in the lung, since
this is the most common methodology in use around the world.
Methods
An application was submitted for a joint European Respiratory Society (ERS) and American Thoracic
Society (ATS) task force to update the 2005 DLCO standards [4] with a particular view to systems using
RGAs. The task force co-chairs were approved by the ERS and the ATS. Task force members were
scientists and physicians with experience in international guidelines, clinical experience of routine lung
function testing and specialist knowledge of gas transfer including research publications. Potential conflicts
of interest were disclosed and vetted. The task force consisted of five members of the task force for the
2005 DLCO standards and four new members. A search using PubMed for literature published between
2000 and 2015 containing various terms related to diffusing capacity and transfer factor yielded 3637
citations. Task force members reviewed the abstracts and identified 113 as relevant to the project and a
further 99 as potentially relevant. All manufacturers of pulmonary function equipment to measure DLCO
were sent a survey requesting equipment specifications. Eight of 13 manufacturers responded. A survey of
DLCO equipment specifications published on the manufacturers’ websites was also conducted. Using the
2005 standards as a base document, revisions and additions were made on a consensus basis. The
recommendations in this document represent the consensus of task force members in regard to the
evidence available for various aspects of DLCO measurement (as cited in the document). Furthermore, it
reflects the expert opinion of the task force members in areas in which peer-reviewed evidence was either
not available or incomplete. The task force also identified areas and directions for future research and
development where evidence is lacking.
Determinants of carbon monoxide uptake

The volume of carbon monoxide in the alveolar space is the product of the alveolar volume (VA) and the
alveolar carbon monoxide fraction (FACO; i.e. the fractional concentration of carbon monoxide in the
alveolar space). Thus, at a constant volume, the transfer of carbon monoxide from the lungs into the blood
is VA·ΔFACO/Δt. Furthermore, in the absence of any carbon monoxide back-pressure in the blood, the
transfer of carbon monoxide is equal to the product of the alveolar carbon monoxide tension (PACO;
i.e. the partial pressure of carbon monoxide) and the DLCO, which is the conductance of carbon
monoxide from the inspired test gas in the alveolar space to binding with haemoglobin (Hb) in the blood
https://doi.org/10.1183/13993003.00016-2016 2
(i.e. flow = pressure × conductance). The combination of these two formulae gives equation 1, which can
be manipulated to give equation 2 for the calculation of DLCO.
VA DFACO =Dt ¼ PACO DLCO (1)
DLCO ¼ VA DFACO =Dt=PACO (2)
The ERS recommends expressing DLCO in SI units (mmol·min−1·kPa−1) while the ATS prefers traditional
units (mL·min−1·mmHg−1) under standard temperature, pressure and dry conditions (STPD). Values in SI
units can be multiplied by 2.987 to obtain values in traditional units.
The capacity of the lung to exchange gas across the alveolar–capillary interface is determined by its
structural and functional properties [1, 7–25]. The structural properties include the following: lung gas
volume; the path length for diffusion in the gas phase; the thickness and area of the alveolar capillary
membrane; any effects of airway closure; and the volume of Hb in capillaries supplying ventilated alveoli.
The functional properties include the following: absolute levels of ventilation and perfusion; the uniformity
of the distribution of ventilation relative to the distribution of perfusion; the composition of the alveolar
gas; the diffusion characteristics of the membrane; the concentration and binding properties of Hb in the
alveolar capillaries; and the carbon monoxide and oxygen tensions in the alveolar capillaries in that part of
the pulmonary vascular bed which exchanges gas with the alveoli.
The process of carbon monoxide transfer from the environment to the pulmonary capillary blood includes
six steps, as follows: 1) bulk-flow delivery of carbon monoxide to the airways and alveolar spaces;
2) mixing and diffusion of carbon monoxide in the alveolar ducts, air sacs and alveoli; 3) transfer of
carbon monoxide across the gaseous to liquid interface of the alveolar membrane; 4) mixing and diffusion
of carbon monoxide in the lung parenchyma and alveolar capillary plasma; 5) diffusion across the red-cell
membrane and within the interior of the red blood cell; 6) chemical reaction with constituents of blood
Hb [13–19].
The process of carbon monoxide uptake can be simplified into two transfer or conductance properties:
1) membrane conductivity (DM), which reflects the diffusion properties of the alveolar capillary
membrane; and 2) binding of carbon monoxide and Hb. The latter can be represented as the product of
the carbon monoxide–Hb chemical reaction rate (θ) and the volume of alveolar capillary blood (VC). Since
these conductances are in series [17], these properties are related as shown in equation 3.
1=DLCO ¼ 1=DM þ 1=uVC (3)
A number of physiological changes can affect DM or θVC to influence DLCO. For example, as the lung
inflates DM increases (largely due to increasing alveolar surface area), while VC effects are variable (due to
differential stretching and flattening of alveolar and extra-alveolar capillaries) [13, 20–27]. The net effect of
these changes is that DLCO tends to increase as the lung inflates but the change in DLCO is proportionally less
than the change in VA [22]. Exercise, the supine position and Müller manoeuvres (inspiratory efforts against
a closed glottis) can all recruit and dilate alveolar capillaries, thereby increasing VC and DLCO [28–34].
Alveolar–capillary recruitment also occurs in the remaining lung tissue following surgical resection, since the
cardiac output now flows through a smaller capillary network. This causes a less than expected loss of VC for
the amount of lung tissue removed. In contrast, Valsalva manoeuvres (expiratory efforts against a closed
glottis) can reduce VC and thereby reduce DLCO [32].
The measurement of carbon monoxide uptake is also affected by the distribution of ventilation with
respect to DM or θVC (i.e. carbon monoxide uptake can only be measured in lung units into which carbon
monoxide was inspired and subsequently expired) [18, 19, 35, 36]. This is particularly important in
diseases such as emphysema, where the inhaled carbon monoxide may preferentially go to the
better-ventilated regions of the lung and the subsequently measured carbon monoxide uptake will be
determined primarily by the uptake properties of these regions. Under these conditions, the tracer gas
dilution used to calculate VA will also reflect primarily regional dilution and underestimate the lung
volume as a whole. The resulting calculated DLCO value should thus be considered as primarily reflecting
the gas-exchange properties of the better ventilated regions of the lung.
In addition to these physiological and distributional effects on DLCO, a number of pathological states can
affect DM, θVC, or both and thereby affect DLCO [8, 9, 37–46]. Measurement of DLCO is used when any of
these pathological processes are suspected or need to be ruled out. Moreover, measuring changes in DLCO
over time in these processes is a useful way of following the course of the disease.
https://doi.org/10.1183/13993003.00016-2016 3
Gas analysers and general equipment

System design
Descriptions of the apparatus and general instructions for performing the single-breath diffusing capacity
manoeuvre are available elsewhere [2, 6, 47–50]. Equipment in clinical use varies widely in complexity but
the basic principles are the same. All systems have a source of test gas, a method of measuring inspired
and expired volume over time and a method of measuring carbon monoxide and tracer gas concentration.
Classical discrete-sample gas-analyser DLCO systems usually display only volume over time but RGA DLCO
systems also provide a continuous recording of carbon monoxide and tracer gas concentration during the
entire test manoeuvre (figure 1).
Equipment requirements
The performance standards for DLCO equipment are summarised in table 1.
Flow and volume analysers

Any error in measuring flow and subsequently calculating volume will produce a correspondingly equal
error in DLCO. However, with continuing improvement in flow measurement technologies, improved
accuracy is being achieved. The flow measurement accuracy over a range of −10 to +10 L·s−1 must be
within ±2%. For calibration with a 3-L syringe, which has a specified maximum error of ±0.5% (i.e. 2.985
to 3.015 L), the calibration volume must be within ±2.5% which is equivalent to an error tolerance of
⩽75 mL. The volume measurement accuracy must be maintained over the range of gas compositions and
concentrations likely to be encountered during DLCO tests.
Gas analysers
For classical discrete sample calculations of DLCO, only the ratios of alveolar to inhaled carbon monoxide
and tracer gas concentrations are needed. Thus, the analysers must primarily be able to produce an output
for measured exhaled carbon monoxide and tracer gas that is a linear extrapolation between the inhaled
(test gas) concentrations and zero (no carbon monoxide or tracer gas present in the analysers) [51, 52]. The
measurement of carbon monoxide and tracer gas concentrations is also a static measurement when
considering a classical discrete sample calculation of DLCO. Analyser response time is not an issue and the
time of gas sample collection is measured separately. Gas concentration digital signal conditioning is not
required to compensate for the response time when calculating DLCO using static measurements.
When nondispersive, infrared carbon monoxide RGAs began to be used to construct a virtual gas sample
from flow and gas concentration data, rather than collecting a physical sample of exhaled gas, no
specifications were mandated other than for the linearity of the gas analysers [5]. However, with RGAs
there is both a lag time (due to the travel of the sampled gas through the sampling tube to the analyser
chamber) and an analyser response time (the time to reach 90% of the actual measurement from the time
the gas sample reaches the analyser) to be considered. As such, the gas concentration signal must be
precisely shifted in time to align with the flow signal (figure 2).
RGA response time

The response time of the RGA will determine how accurately the analyser is able to track the true carbon
monoxide and tracer gas concentrations. The most rapid changes in concentration occur at the start of test
Gas concentration % (full scale)
5 100
4
Tracer gas
Volume L
2 Carbon
monoxide
1
0 0
0 2 4 6 8 10 12 14 16
Time s
FIGURE 1 Diagram of lung volume and gas concentration during the single-breath manoeuvre to measure the
uptake of carbon monoxide. Whereas classical DLCO systems only display the volume–time graph, rapid gas
analyser (RGA) DLCO systems also display the carbon monoxide and tracer gas concentrations throughout the
single-breath manoeuvre. Reproduced from [4].
https://doi.org/10.1183/13993003.00016-2016 4
TABLE 1 Equipment specifications and performance standards
DLCO System Specification

Required Recommended
Rapid gas analyser systems

Analyser specification
0–90% response time (see figure 2) ⩽150 ms
Maximum nonlinearity ±1% of full scale
Accuracy Within ±1% of full scale
Interference from 5% carbon dioxide or 5% water vapour ⩽10 ppm error in [CO]
Drift for carbon monoxide ⩽10 ppm over 30 s
Drift for tracer gas ⩽0.5% of full scale over 30 s
Flow accuracy Within ±2% over the range of
−10 to +10 L·s−1
Volume accuracy (3-L syringe check) Within ±75 mL
Barometric pressure sensor accuracy Within ±2.5%
Ability to perform a QA check (3-L syringe; ATP Calculate total volume (VA) of 3±0.3 L and
mode; inhaling ∼2 L test gas) DLCO of <0.5 mL·min−1·mmHg−1 or
<0.166 mmol·min−1·kPa−1
Sample and store data with adequate resolution Digitise at ⩾100 Hz Digitise at 1000 Hz
per channel with ⩾14 bit resolution
Monitor and report end-expiratory tracer gas and carbon Implemented#
monoxide concentrations (alert operator if washout is
incomplete)
Compensate for end-expiratory gas concentrations prior Implemented#
to test gas inhalation in the calculation of VA and DLCO
Ensure proper alignment of gas concentration signals and the Implemented#
flow signal
Measure anatomic dead-space using the Fowler Implemented#
method (see figure 6)
Display a graph of gas concentration versus expired volume to Implemented#
confirm the point of dead-space washout and report the
amount of manual adjustment if done (see figure 4)
Measure VA using all of the tracer gas data from the entire Implemented#
manoeuvre in the mass balance equation
Report the DLCO adjusted for the change in PAO2 due to Implemented#
barometric pressure
Ability to input simulated digital test data and compute DLCO, VA, Calculate values within 2%
TLC, VD of actual values
Report the DLCO adjusted for the change in PAO2 due to PACO2, if the Implemented#
carbon dioxide concentration signal is available
Classical discrete sample systems
Analyser specification
Maximum nonlinearity ±1% of full scale
Accuracy Within ±1% of full scale
Interference from 5% carbon dioxide or 5% water vapour ⩽10 ppm error in [CO]
Drift for carbon monoxide ⩽10 ppm over 30 s
Drift for tracer gas ⩽0.5% of full scale over 30 s
Flow accuracy Within ±2% over the range of
−10 to +10 L·s−1
Volume accuracy (3-L syringe check) Within ±75 mL
Ability to perform a QA check (3-L syringe; ATP mode; Calculate total volume (VA) of 3±0.3 L
inhaling ∼2 L test gas) and DLCO of <0.5 mL·min−1·mmHg−1 or
<0.166 mmol·min−1·kPa−1
DLCO: diffusing capacity of the lung for carbon monoxide; [CO]: carbon monoxide concentration; QA: quality assurance; ATP: ambient temperature,
pressure and humidity; VA: alveolar volume; PAO2: alveolar oxygen tension; PACO2: alveolar carbon dioxide tension; TLC: total lung capacity;
VD: dead-space volume. #: Implemented means that the manufacturer has implemented the designated functionality in the DLCO system.
gas inhalation and at the start of exhalation following the breath-hold. Even after the application of an
appropriate time shift (see below) to correct for lag time and analyser response time, there will be a
residual error in DLCO due to the finite response time. For every 100 ms increase in the 0–90% response
https://doi.org/10.1183/13993003.00016-2016 5
100
t0–90%
90
Concentration % (full scale)

80
70 Flow 10
Flow L·s–1
60 Shift
50
40 0
30
20
Carbon monoxide
10 Lag time
0
0 200 400 600 800 1000
Time ms
FIGURE 2 Lag and response times for carbon monoxide: the response time of the analyser was estimated by
rapidly switching the gas being sampled from zero to full-scale carbon monoxide. The change in the flow
signal shows the time at which the switch was made from medical air to test gas. The lag time, the 0–90%
response time and the optimal shift are calculated from the resulting response curve.
time, the error in DLCO increases by about 0.7% [53]. Based on the above considerations, the 0–90%
response time for RGAs used in DLCO systems must be ⩽150 ms.
Response time can be improved by reducing the volume of the analyser chamber and increasing the
sample aspiration rate: however, such measures can cause a deterioration of the signal by creating more
noise. The use of signal conditioning to simulate a more rapid analyser response may also introduce more
noise and errors into the signal. Digital conditioning techniques should only be used to digitally enhance
response time if they do not compromise signal quality and accuracy and serve to preserve or improve
DLCO measurement accuracy.
Linearity and accuracy

The linearity of gas concentration signals is of primary importance in measuring DLCO since the ratios of
the gas concentrations are considered in the classical calculations [50, 52]. The error in DLCO measurement
due to nonlinearity in these signals depends on the size of the lungs and the rate of uptake of carbon
monoxide. A nonlinearity of 0.5% of full scale can cause errors ranging from 0.5% in a subject with a DLCO
of 13.4 mmol·min−1·kPa−1 (40 mL·min−1·mmHg−1) to 1.7% in a subject with a DLCO of
3.35 mmol·min−1·kPa−1 (10 mL·min−1·mmHg−1) [53]. The manufacturer specification for analyser linearity
is that any nonlinearity must not exceed 0.5% of full scale once zero and full scale values have been set. The
accuracy of the gas analyser signal also becomes important when measuring the residual background
alveolar carbon monoxide concentration and the washout of tracer gas from the previous DLCO manoeuvre.
The output of the gas analyser must be accurate to within ±1% of full scale.
Interference and noise

Nondispersive, infrared carbon monoxide analysers typically have some cross sensitivity to carbon dioxide
and water vapour. Strategies to reduce and/or compensate for cross sensitivity are required such that the
water vapour and carbon dioxide in exhaled gas (up to 5% each; i.e. water vapour pressure (PH2O)
6.28 kPa/47 mmHg) contribute a less than 10 ppm error in the measured carbon monoxide signal.
Measuring the exhaled gas from the subject prior to the inhalation of test gas can also provide an offset
due to carbon dioxide and water vapour measurements that can be used to adjust the concentration signal.
Drift
Gas analysers should have only minimal drift in zero and gain, such that output is stable over the test
interval. Gas analyser drift must be ⩽10 ppm over 30 s for carbon monoxide and ⩽0.5% of full scale over
30 s for tracer gas. It is recommended that manufacturers provide an optional test mode to display the
measured gas concentrations so that stability can be confirmed. Any drift must be determined by
comparing the carbon monoxide and tracer values measured in room air immediately prior to and
immediately following the single-breath manoeuvre. The gas concentration signals used in the calculation
of DLCO must be compensated for drift, assuming a linear change over the measurement interval.
Aspiration flow
Depending upon the design of the breathing circuit, the gas analyser sampling port and the gas analyser
aspiration flow, gas may be entrained into the sampling line from room air or from the test gas when the
https://doi.org/10.1183/13993003.00016-2016 6
exhaled flow decreases to near zero at the end of exhalation. Clearly, when the subject’s exhaled flow drops
below the aspiration flow, the sample will entrain other gas that is not part of the exhaled gas. DLCO
instrument manufacturers are required to determine the lowest exhaled flow at which the gas sampling
line will not entrain gas other than exhaled gas. This flow must be reported in the system specifications. In
the analysis of the exhaled gas concentration data, measurements of gas concentration below the specified
flow must not be included in either the determination of washout of tracer gas from a previous manoeuvre
(see the section on interval between manoeuvres below) or the calculation of absolute end-expiratory lung
volume (Vee) in equations 22 and 25 below.
Digitisation
In order for the digitised signal to accurately track the gas concentration signal and in order to provide
adequate opportunity for signal processing for data alignment, the minimum signal sampling rate must be
⩾100 Hz per channel: however, a rate of 1000 Hz is recommended. The analogue to digital converter
resolution must be ⩾14 bits.
Other equipment considerations

Circuit resistance must be <1.5 cmH2O·L−1·s−1 up to 6 L·s−1 flow. If a demand-flow regulator is used on a
compressed test gas cylinder, the maximal inspiratory pressure required for 6 L·s−1 inspiratory flow
through both the circuit and the valve must be <9 cmH2O.
Equipment dead-space volume (VDequip) for both inspired test gas and the alveolar sample must be known
and their role in all data computation algorithms must be identified and documented. For adults, the
VDequip including the breathing circuit proximal to the gas analyser sampling point, filter and mouthpiece
must be <200 mL. Smaller dead-space volumes are recommended for paediatric applications and people
with a vital capacity (VC) of less than 2 L.
The system must be leak free; this is particularly important for DLCO systems that aspirate gas samples
through the gas analyser at sub-atmospheric pressures. When samples are aspirated, leaks in tubing,
fittings and other locations allow room air to be drawn into the gas circuit, thus diluting the sample and
reducing the concentrations of carbon monoxide and tracer gases.
Equipment calibration and quality control

The considerations for equipment calibration and quality control are illustrated in table 2. There are a
number of regular procedures to apply, summarised as follows:
1) Flow and gas analysers must be zeroed prior to each manoeuvre. After each manoeuvre, a new zeroing
procedure must be carried out to account for analyser drift during the previous test.
2) Each day, prior to testing, there must be a volume calibration check with a 3-L syringe [54]. The syringe
should be discharged at least three times to give a range of flow rates varying between 0.5 and 12 L·s−1
(with 3-L injection times of ∼6 s and ∼0.5 s, respectively). The volume at each flow rate must meet an
accuracy requirement of ⩽2.5% error. For devices using disposable flow sensors, a new sensor from the
supply used for patient tests must be tested each day. The calibration check may need to be repeated
during the day if ambient conditions change. Newer systems monitor ambient conditions and make
adjustments as necessary or produce a calibration alert when needed. Older systems may require a
calibration check if room temperature changes by more than 3 °C or relative humidity changes by more
than 15% (absolute). Operators should also perform a calibration check whenever they notice significant
TABLE 2 Equipment calibration schedule
Calibration technique Frequency
Flow analyser zeroing Before each test

Gas analyser zeroing Before/after each test
Volume calibration check Daily
Biologic control Weekly
Calibration syringe DLCO check Weekly
Calibration syringe leak test Monthly
Linearity check (calibration syringe or simulator) Monthly
DLCO: diffusing capacity of the lung for carbon monoxide.
https://doi.org/10.1183/13993003.00016-2016 7
discrepancies between the inspired volume (VI) and VC, or between VA and total lung capacity (TLC),
which might suggest volume calibration problems.
3) Each week, or whenever problems are suspected, the following procedures must be followed. First, for
those DLCO systems using a volume-type spirometer, a spirometer leak test should be performed according
to the manufacturer’s specifications. Secondly, a DLCO test should be performed with a calibrated 3-L syringe
by attaching the syringe to the instrument in the normal patient test mode. The syringe should then be
emptied, filled with 3 L of test gas and emptied into the mouthpiece after the 10 s breath-hold. The
calculation of VA must be within 300 mL of 3 L times the STPD to BTPS (body temperature, ambient
pressure, saturated with water vapour conditions) correction factor, which is 863/(PB−47), where PB is the
barometric pressure. It should be noted that a 3-L calibration syringe will have an additional dead-space
which, depending on the connection to the mouthpiece, is typically ∼50 mL and must be considered in the
VA calculation. The absolute value of the calculated DLCO must be <0.166 mmol·min−1·kPa−1 or
<0.5 mL·min−1·mmHg−1. Thirdly, a test should be performed on a “standard subject” (biological control) or
simulator [55]. Standard subjects are nonsmokers who have been found to have a consistently repeatable
DLCO (e.g. healthy laboratory personnel). If the DLCO in a standard subject varies either by >12% or by
>1 mmol·min−1·kPa−1 (>3 mL·min−1·mmHg−1) from the mean of previous values, the test must be repeated.
A study of the long-term intersession variability of DLCO has found that biological control deviations either
>12% or >3 mL·min−1·mmHg−1 from the average of the first six tests indicate that the instrument is not
within quality control limits and must be carefully evaluated before further patient testing [56]. For a digital
system check of the DLCO calculation algorithm, standardised digital data for flow, volume and carbon
monoxide and tracer gas concentration will be developed by the task force and made available with a sample
rate of 1 kHz as an xml or csv file. It is strongly recommended that manufacturers provide the ability to
input data from such a file and generate test results to compare measured versus known DLCO and VA values.
For systems failing the above testing, the DLCO system must be evaluated carefully for the possibility of leaks,
nonlinear analyser function, and volume and time inaccuracy, etc. When sufficient data on a standard
individual have been obtained, laboratories should establish their own outlier criteria to serve as indicators of
potential problems with their DLCO systems. Manufacturers are encouraged to develop automated
quality-control software to assist and enhance the utility of these steps.
4) Each month a leak test of the 3-L calibration syringe should be performed. If the calibration syringe
does not have a volume scale on the shaft, mark 50 mL below full by measuring the excursion of the shaft
from 0 to 3 L and marking it at a distance that is 0.017 of the full excursion. Fill the syringe and place a
stopper at the syringe input. Push the syringe in to the 50 mL mark (which generates a pressure of about
17 cmH2O), hold for 10 s and release. If the syringe does not return to within 10 mL of the full position, it
should be sent for repair. The procedure is then repeated starting with the syringe at 50 mL below full,
applying the stopper and pulling the syringe to the full position.
5) Each month, gas-analyser linearity should be assessed. A straightforward approach is to measure known
serial dilutions of the test gas [57], or to measure the concentration of a separate high-precision test gas
having a certificate of analysis. Manufacturers must be encouraged to automate this function. For systems
with independent measurement of carbon monoxide and tracer gas, the analyser linearity may also be
assessed by comparing the ratio of carbon monoxide and tracer gas concentration to arbitrary dilutions of
test gas with room air. A third type of calibration syringe test, which differs from the volume check in
point two and the DLCO check in point three by using the 3-L syringe in ambient temperature, pressure
and humidity (ATP) mode, may also reveal problems with analyser linearity. With approximately 1 L of
air in the syringe, the test begins by filling the remaining volume with test gas. Following a 10 s
“breath-hold” the syringe is then emptied. The calculation of VA must be within 300 mL of 3 L with the
syringe dead-space being used for the anatomic dead-space in the VA calculation. The absolute value of
DLCO must be <0.166 mmol·min−1·kPa−1 or <0.5 mL·min−1·mmHg−1. A review of quality control data for
four different DLCO systems between 2006 and 2015 using this procedure found only four outlier points
where |DLCO| was >0.13 mmol·min−1·kPa−1 (>0.4 mL·min−1·mmHg−1). The same data showed that VA was
consistently within 3±0.3 L for the four systems (unpublished data from B.R. Thompson). Gas mixing in
the syringe can be improved by using low flow rates and extending the breath-hold time. The effects of
incomplete mixing in the syringe can be minimised by using a larger sample volume. In the absence of a
DLCO simulator and high-precision test gases, system checks must be performed using a 3-L calibrating
syringe in ATP mode. Manufacturers must provide this test option, which will be the same as the usual
testing procedure for a patient, with the exception that VA will be reported in ATP rather than BTPS.
6) A record of equipment checks and standard subject tests should be dated and kept in a laboratory log
book or digital file folder. Manufacturers are encouraged to provide software and test equipment options
for quality control measurement and quality control data management. In addition, manufacturers may
provide equipment-specific, quality-control measures in addition to the foregoing points. If water vapour
https://doi.org/10.1183/13993003.00016-2016 8
permeable tubing is used to either remove water vapour or equilibrate water vapour with room air, such
tubing must be replaced according to manufacturer recommendations to ensure that it is functioning
properly. Chemical gas analyser cells will have a replacement schedule. Manufacturers may also have
preventative maintenance schedules for various other system components (e.g. balloon valves) which will
require testing and replacement as necessary.
Quality control for RGA systems

Modern DLCO systems are completely integrated and do not use stand-alone gas analysers that can be
tested separately. Specifications for manufacturers are required to facilitate a uniform testing and
calibration strategy across all systems. Quality-control requirements include analogue testing with devices
such as a simulator [58], the option to operate in full ATP mode and a digital calibration option to verify
the computational algorithms. The digital calibration option should use simulated flow, carbon monoxide
concentration and tracer gas concentration data from standardised manoeuvres with a known DLCO.
Infection control
The major goal of infection control is to prevent the transmission of infection to patients and staff during
pulmonary function testing. The recommendations in the ATS/ERS documents for spirometry and general
considerations for pulmonary function testing also apply to DLCO equipment and procedures [59–61].
Standardisation issues in the single-breath testing technique

The single-breath determination of DLCO involves measuring the uptake of carbon monoxide from the
lung over a breath-holding period. To minimise variability as much as possible, the following specifications
for the standardisation of testing techniques are provided.
Patient condition
Factors that affect VC (e.g. exercise, body position, Hb affinity for carbon monoxide, alveolar oxygen
tension (PAO2), and level of carboxyhaemoglobin (COHb)) must be standardised. If clinically acceptable,
the subject should not breathe supplemental oxygen for ⩾10 min prior to a DLCO manoeuvre. In addition,
when using exercise or the supine position to assess the ability of the lung to increase gas transfer [18, 28–
31], the level of exercise and/or the duration of the supine position must be noted. Before beginning the
test, the manoeuvres must be demonstrated and the subject carefully instructed. Furthermore, the subject
must be seated comfortably throughout the test procedure, which must be performed at a stable,
comfortable temperature within the manufacturer’s equipment specifications.
COHb produces an acute, reversible decrease in DLCO [62–66], largely due to its effects on carbon
monoxide back-pressure and the “anaemia effect” from decreased Hb binding sites for test gas carbon
monoxide. As cigarette smoking is the most common source of COHb, subjects must be asked to refrain
from smoking or other sources of carbon monoxide exposure on the day of the test. The time of the last
cigarette smoked must be recorded and noted for the interpretation. A correction for carbon monoxide
back-pressure must be made for recent or heavy cigarette smoking (see the section on adjustment for
COHb concentration and carbon monoxide back-pressure below). Air pollution may also result in higher
COHb levels and exposure to high levels of air pollution should be noted.
Inspiratory manoeuvres
Once the mouthpiece and nose clip are in place, tidal breathing must be carried out for a sufficient time to
assure that the subject is comfortable with the mouthpiece and that the nose clips and mouthpiece are
used appropriately with no leaks. The DLCO manoeuvre begins with unforced exhalation to residual
volume (RV). In obstructive lung disease, where exhalation to RV may require a prolonged period, a
reasonable recommendation is that this portion of the manoeuvre must be limited to <12 s. Exhalation
times of up to 12 s will allow most patients with airflow obstruction to exhale sufficiently such that they
can achieve a maximal VC for the subsequent inhalation of test gas. Submaximal inhalation occurs most
frequently in patients with airflow obstruction who are not given adequate time to exhale prior to the
inhalation of test gas.
At RV, the subject’s mouthpiece is connected to a source of test gas, and the subject inhales rapidly to TLC.
A submaximal inspired volume of test gas (i.e. less than the known VC) can affect carbon monoxide
uptake depending upon whether it is a result of an initial suboptimal exhalation to RV (manoeuvre
performed at TLC) or whether it is due to a suboptimal inhalation from RV (manoeuvre performed below
TLC) [22–25]. In the former case, the calculated VA and DLCO will accurately reflect lung volume and the
carbon monoxide uptake properties of the lung at TLC. In the latter case, the VA will be reduced and
DLCO measurement will be affected.
https://doi.org/10.1183/13993003.00016-2016 9
Due to these effects, it is important that the inspired volume of test gas, VI, be as close to the known VC
as possible. Data from a large patient population have shown that the VI during DLCO measurement
averages ∼90% of the VC [22]. Since the introduction of the 2005 guidelines and subsequent
implementation of quality-control checks by equipment manufacturers, there has been an improvement in
test quality such that 90% of the largest known VC as the lower limit of acceptability for VI has been
shown to be attainable [67]. Furthermore, as noted above, VI will be improved by allowing up to 12 s for
exhalation prior to inhalation of test gas. VI must be at least 90% of the largest VC in the same pulmonary
function testing session. However, a manoeuvre may be deemed to be acceptable if VI is within 85% of the
largest VC and the VA is within 200 mL or 5% (whichever is greater) of the highest VA among acceptable
DLCO manoeuvres.
The inspiration must be rapid, since the DLCO calculations assume instantaneous lung filling [27, 68–74].
Slower lung filling decreases the amount of time the lung is at full inspiration with a consequent reduction in
carbon monoxide uptake. Although various sample timing techniques address the issue of lung filling and
emptying time, inspiration of test gas should be sufficiently rapid such that that 85% of VI must be inspired
in <4.0 s. If longer inspiratory times are needed to inspire 85% of VI, this must be noted on the test report.
Breath-hold and expiratory manoeuvres

During the breath-hold, both the Valsalva and Müller manoeuvres (expiratory or inspiratory efforts against
a closed glottis, respectively) can affect DLCO calculation by decreasing or increasing thoracic blood
volume, respectively, resulting in a corresponding decrease or increase in DLCO, respectively, for each
manoeuvre [32, 75, 76]. The intrapulmonary pressure during the breath-hold should thus be near
atmospheric and this is best accomplished by having the subject voluntarily maintain full inspiration using
only the minimal necessary effort. The breath-hold time must be 10±2 s, a target easily achieved in the
vast majority of subjects [77].
As with inspiration, the DLCO calculation assumes instantaneous lung emptying [27, 68–72]. Although
various sample timing techniques address the fact that emptying is not instantaneous, it is still reasonable
to expect that the expiratory manoeuvre must be smooth, unforced and without hesitation or interruption.
Transient Possible
overshoot exhaled
gas leak
Volume L
Stepwise inhalation
or exhalation
Inhalation
too slow Exhaled volume larger
than inhaled volume
Time s
Gas concentration % (full scale)
Breath-hold leak
Methane
Inspiratory Carbon
leak monoxide
Time s
FIGURE 3 Potential problems with the breathing manoeuvre for single-breath diffusing capacity of the lung
for carbon monoxide that can lead to measurement errors. Reproduced from [4].
https://doi.org/10.1183/13993003.00016-2016 10
For classical systems, the exhalation time for washout and discrete sample collection should not exceed 4 s.
In subjects who require a longer expiratory time to provide an appropriate alveolar gas sample, the
expiratory time must be noted in the test report. For RGA systems, exhalation should continue to RV, with
a maximum exhalation time of 12 s, which provides improved measurement of VA as noted in the data
analysis for RGA systems section below. The results of common errors that can occur during the
inspiration, breath-hold and expiration manoeuvres are illustrated in figure 3.
Washout and sample collection manoeuvres

DLCO calculations (see the calculations section below) are performed by analysis of discrete alveolar gas
samples containing carbon monoxide and tracer gas. During expiration, a volume of gas must be expired
to clear the total anatomical and equipment dead-space volume (VD) and then discarded before the
alveolar sample is collected (figure 1). Collecting an alveolar gas sample before the point of dead-space
washout will underestimate DLCO, while delaying sample collection beyond the point of dead-space
washout will overestimate DLCO [68, 72].
Washout and sample collection in classical systems

The washout volume must be 0.75–1.0 L (BTPS). If the patient’s VC is <2.00 L, the washout volume may
be reduced to 0.50 L. The discrete-sample gas volume (VS) is the volume of gas collected following the
breath-hold and used to analyse alveolar carbon monoxide and tracer gas concentrations. VS collection
time will affect the measurement of breath-hold time (see below). For discrete sample systems that require
larger sample volumes, a VS of 0.5–1 L should be collected for analysis. In patients with a VC <1 L, a VS
<0.5 L may be used if it can be confirmed that the dead-space has been cleared.
Washout and sample collection in RGA systems

The time point for dead-space washout can be determined from the expired tracer gas concentration data
using an objective algorithm. The beginning of the alveolar plateau can be located by determining the
a) c)
100 100
Tracer gas Tracer gas
50 50
Carbon
Carbon
monoxide
monoxide
0 0
10 11 12 13 14 15 16 17 10 1 2 3 4 5 6
Time s Volume L
b) d)
100 100
Tracer gas Tracer gas
50 50
Carbon Carbon
monoxide monoxide
0 0
10 11 12 13 14 15 16 17 0 1 2 3 4 5 6
Time s Volume L
FIGURE 4 Comparison of gas concentration plotted as a function of time (a and b) or volume (c and d) for
carbon monoxide and tracer gas. The shaded bar shows the collection of a 500-mL sample of exhaled gas. The
upper panels (a and c) show sample collection as selected by computer algorithm (based on gas concentration
and lung volume). The lower panels (b and d) show sample collection after manual adjustment by an operator
using the concentration versus time plot. Operators tend to be more conservative and may over-shift the
sample. When gas concentration is plotted against time, the shift does not appear to be significant; however,
when gas concentration is plotted against volume, the degree of shift becomes more apparent.
https://doi.org/10.1183/13993003.00016-2016 11
breakpoint of each phase of the washout on a plot of concentration versus volume and adding a
proportion of the dead-space volume measured by the FOWLER technique [78] to the phase II to III
breakpoint [79]. Such an approach can be automated; however, for visual verification of the point of
dead-space washout, the tracer gas concentration must be displayed as a function of volume, since
verifying the point of dead-space washout using the concentration versus time curve can be deceptive due
to the relatively high flow at the beginning of exhalation. This is illustrated in figure 4. If the sample
collection point is changed by the operator, it must be recorded in the database and on the report.
With RGA systems, the concentrations of carbon monoxide and tracer gas in a virtual alveolar gas sample
are calculated for use in measuring DLCO. The gas concentrations in a virtual sample, that would have
been observed in a sample of a given volume had it been collected at a given point during exhalation, are
calculated from the flow and gas concentration data. A virtual 200-mL sample analysed by the method of
JONES and MEADE [72] has been found to be robust [68]. However, these systems are capable of simulating
much smaller gas samples and JONES and MEADE [72] used 85-mL gas samples in the development of their
method. Smaller virtual samples will be more affected by noise in the expired carbon monoxide
concentration signal. Virtual alveolar gas sample volumes of 85 mL to 500 mL may be used.
Inspired gas composition

The test gas used to calculate DLCO should contain very close to 0.3% carbon monoxide, 21% oxygen, a
tracer gas and a balance of nitrogen. The tracer gas must be relatively insoluble and relatively chemically
and biologically inert. Since the tracer gas is used to determine the initial alveolar carbon monoxide
concentration, as well as the VA from which carbon monoxide uptake is occurring, its gaseous diffusivity
should be similar to carbon monoxide and it should not interfere with the measurement of carbon
monoxide concentration. The tracer gas should also not ordinarily be present in alveolar gas or else be
present at a known, fixed concentration (e.g. argon).
Commonly used tracer gases include helium and methane. Helium meets most of the previous criteria;
however, its gaseous diffusivity is considerably higher than that of carbon monoxide. Methane is
commonly used for RGA systems; its gaseous diffusivity is closer to carbon monoxide but it has a slightly
higher liquid solubility than helium. A recent study has found no clinical difference in DLCO using either
helium or methane in normal subjects or patients with COPD [80].
As noted above, the inspired carbon monoxide concentration should be close to 0.3%; however, as ratios
are more important than absolute values, exact concentrations are not critical. The assumption in
calculating carbon monoxide uptake is that capillary blood does not contain carbon monoxide. Thus,
corrections are needed in patients who have significant COHb (see the section on adjustment for COHb
concentration and carbon monoxide back-pressure below). There are two considerations influencing the
rationale for recommending an inspiratory oxygen fraction (FIO2) of 21% in the test gas for routine DLCO
testing. First, the majority of studies developing reference values for DLCO, which are based on the 2005
standards [4], use an FIO2 of 21% (see the section on reference values below). Secondly, the PAO2 following
a maximal inhalation will depend on the dead-space volume and the ratio of VI to VA for any given value
of FIO2 in the test gas. Hence, if reducing FIO2 in the test gas is intended to simulate tidal breathing
conditions (i.e. a PAO2 of 100 mmHg or 13 kPa), it may not do so in all subjects.
Although not performed routinely, the measurement of DLCO at several different levels of PAO2 allows the
two components of DLCO (DM and θVC) to be distinguished. This is accomplished by using the
Roughton–Forster relationship noted previously (equation 3) and varying θ by altering PAO2. Subsequently,
1/DLCO is plotted against 1/θ at the different PAO2 levels. The slope of this relationship is 1/VC and the
intercept is 1/DM. While there are differences in the proposed value of θ, it is beyond the scope of this
report to make recommendations for the value of θ to be used.
Manoeuvre intervals
Manoeuvre intervals in classical systems
The 2005 ERS/ATS recommendations state that at least 4 min must be allowed between manoeuvres to
allow for adequate elimination of test gas from the lungs. The subject should remain seated during this
interval. In patients with airflow obstruction, a longer period (e.g. 10 min) should be considered. Several
deep inspirations during this period may help to clear test gases more effectively.
Manoeuvre intervals in RGA systems

Exhaled gas can be monitored as soon as the subject begins breathing through the mouthpiece prior to the
inhalation of test gas. If a previous manoeuvre was conducted, the information collected on end-expiratory
tracer gas levels will indicate whether or not washout is complete, which may occur in less than 4 min in
some subjects. For complete washout, the tracer gas level at end-exhalation must be ⩽2% of the tracer gas
https://doi.org/10.1183/13993003.00016-2016 12
concentration in the test gas. Occasionally, if a subject has not reached this level of washout after 5 min,
the operator may have the option of continuing with the next manoeuvre. However, in either event, the
end-expiratory tracer gas concentration must be reported and used to adjust the tracer gas concentration
data used in the determination of VA at the beginning of breath-holding.
The carbon monoxide concentration measured in exhaled gas prior to inhaling test gas can be used for
three important purposes [53]: 1) to adjust DLCO calculations for the back-pressure of carbon monoxide,
both the ambient level and the increase that occurs with multiple DLCO manoeuvres; 2) to estimate the
COHb concentration and adjust the DLCO calculation accordingly; and 3) to compensate for any residual
effects of water vapour and carbon dioxide on the carbon monoxide analysers.
Miscellaneous factors
There may be a diurnal variation in DLCO, since one study has found that DLCO falls 1.2–2.2% per hour
throughout the day [81]. The reason for this change is not clear and is not explained by carbon monoxide
back-pressure or changes in VA, VI, or breath-hold time. One explanation is a combination of changes in
carbon monoxide back-pressure and diurnal variation in Hb concentration [82]. A 13% change in DLCO
during the menstrual cycle has been reported [83]. The highest value is observed just before the menses and
the lowest is observed on the third day of menses; however, it is not clear if this is simply a Hb effect or
whether it reflects other physiological processes (e.g. hormonal changes on pulmonary vascular tone). Ingestion
of ethanol has been reported to decrease DLCO [84, 85]. The mechanisms involved are not clear, although it is
known that some fuel-cell carbon monoxide analysers are sensitive to exhaled ethanol and ketones.
Pulmonary function test sequence

DLCO manoeuvres are frequently conducted immediately following the administration of 400 μg of
salbutamol in the interval between pre- and post-bronchodilator spirometry testing [60]. While an older
study in obstructive lung disease subjects found that DLCO may increase by up to 6% after administration
of a bronchodilator [86], a newer study has found that the administration of 400 μg of salbutamol has no
significant effect on DLCO in normal control subjects or in patients with either reversible on non-reversible
airflow obstruction [87]. A further study has found no significant salbutamol effect on DLCO in COPD
patients at doses of less than 1000 μg [88]. Therefore, there is no recommendation against use of a
bronchodilator prior to DLCO tests.
Spirometry is a form of exercise [59], which could conceivably impact on DLCO values; however, no
studies were found which support a recommendation for a rest interval following spirometry. If the order
of testing includes measuring absolute lung volumes using nitrogen washout, during which 100% oxygen
is inspired [89] prior to DLCO manoeuvres, ample time is required for alveolar oxygen levels to return to
normal. For nitrogen to wash back in to normal levels, allow a rest interval equal to twice the time
required for the nitrogen washout test to be completed [90]. It is recommended that DLCO measurements
be made before any multi-breath nitrogen washout tests.
Calculations
Calculating diffusing capacity
Converting equation 2 to calculus notation and using PACO=FACO·(PB−PH2O), where FACO is the alveolar
carbon monoxide fraction in the dry gas, PB is the barometric pressure and PH2O is the water vapour
pressure, gives equation 4 as shown below.
d(VA FACO )
¼ DLCO FACO (PB PH2 O ) (4)
dt
Assuming a constant volume and that the pulmonary capillary carbon monoxide tension is near zero,
solving for DLCO gives equation 5, where FACO,0 and FACO,t are the fractional concentrations of carbon
monoxide in the alveolar volume at time 0 and time t, respectively. The rate of gas uptake is expressed in
mL(STPD)·min−1 and the transfer gradient (the difference between the alveolar and pulmonary capillary
pressures) in mmHg. Therefore, DLCO has traditional units of mL(STPD)·min−1·mmHg−1 and SI units of
mmol(STPD)·min−1·kPa−1.

VA FACO,0
DLCO ¼ ln (5)
t (PB PH2 O ) FACO,t
The single-breath DLCO technique assumes that both carbon monoxide and the tracer gas are diluted
equally on inspiration. Thus, the initial alveolar concentration of carbon monoxide at the theoretical start
https://doi.org/10.1183/13993003.00016-2016 13
of breath-holding (FACO,0) can be calculated by knowing the inspired tracer gas fraction (FITr) and the
alveolar tracer gas fraction (FATr). In this case, if FICO is the carbon monoxide fraction in the inspired test
gas, we can generate equation 6.
FATr
F ACO,0 ¼ F ICO (6)
F ITr
Tracer gas dilution is also used to determine the effective VA. If we solve for DLCO we can generate
equation 7, where VA is reported in L (BTPS) and tBH, the breath-hold time, is reported in seconds.

VA F ICO F ATr
DLCO ¼ ln (7)
tBH (PB PH2 O ) FACO F ITr
If we convert VA to STPD conditions we obtain equation 8 for traditional units of DLCO

(VA mL(STPD)·min−1·mmHg−1). The factor of 60 000 arises from the change to the traditional units (60 s
to 1 min and 1 L to 1000 mL).

VASTPD F ICO FATr
DLCO ¼ ln 60 000 (8)
tBH (PB 47) FACO F ITr
If we then convert to SI units we obtain equation 9 (units of TLCO: mmol·min−1·kPa−1), where the factor
of 22.4 arises from the conversion of mL(STPD) to mmol.

VASTPD F ICO FATr
TLCO ¼ ln 60 000=22:4 (9)
tBH (PB 6:28) FACO F ITr
Calculating breath-hold time

The breath-hold time, or time of transfer during which carbon monoxide changes from its initial to its
final concentration (tBH), is part of the denominator in the DLCO equation (equation 7). As noted
previously, the single-breath measurement of carbon monoxide uptake assumes an instantaneous lung
filling and emptying process. However, both inspiration and expiration require up to several seconds, and
these periods of changing gas volume in the lung must be accounted for in the calculations. For purposes
of standardisation, the method of JONES and MEADE (figure 5) [72] is recommended, since it has the
theoretical appeal of empirically accounting for the effects of inspiratory and expiratory time. This method
has also been shown to adequately address inspiratory flows as low as 1 L·s−1, breath-hold times as short
as 5 s and expiratory flows as low as 0.5 L·s−1 in normal subjects [68] when using an RGA system that
Inhalation Breath-holding Exhalation

5
tI TLC
90% VI Washout volume
4
Sample volume
Volume L
3 VI
tBH
1
RV
0
0 2 4 6 8 10 12 14 16
Time s
FIGURE 5 Schematic illustration of measuring breath-hold time for the single-breath diffusing capacity of the
lung for carbon monoxide. The JONES and MEADE [72] breath-hold time includes 0.7 of inspiratory time and half
of sample time. VI: inspired volume; tI: time of inspiration (defined from the back-extrapolated time 0 to the
time that 90% of the VI has been inhaled); tBH: breath-hold time; TLC: total lung capacity; RV: residual volume.
Reproduced from [4].
https://doi.org/10.1183/13993003.00016-2016 14
measures the dead-space and calculates VA using the tracer gas concentration data from the entire
manoeuvre. With the approach taken by JONES and MEADE [72], breath-hold time equals the time starting
from 0.3 of the inspiratory time (tI) to the middle of the sample collection time. As in spirometry, the
back-extrapolation technique must be used to establish time zero [2, 59]. The time when 90% of the VI
has been inspired is a reasonable end-point for defining inspiratory time (figure 5).
Calculating the alveolar volume

Alveolar volume in classical systems
VA represents an estimate of lung gas volume into which carbon monoxide is distributed and then
transferred across the alveolar capillary membrane [1, 6] and is thus critical in the measurement of DLCO.
Classical DLCO equipment collects an actual sample of exhaled gas for analysis and determination of the
carbon monoxide and tracer gas concentrations. Since there is only one measurement, the alveolar volume
is calculated from the same sample that is used for analysis of carbon monoxide uptake [2]. As noted
elsewhere, JONES and MEADE [72] have shown that the sample has to be small (85 mL) to reduce errors in
DLCO determination. The calculation of VA requires an assumption that the alveolar gas is completely
mixed at the maximal lung volume and that a small sample of exhaled gas will presumably be
representative of the entire lung. In normal subjects this assumption is reasonable and has little effect on
the measurement of VA. However, in patients whose lung disease results in a heterogeneous distribution of
ventilation, the size and timing of the sample have a major effect on the measurement of VA. For classical
systems, VA is determined from values for VI, FITr and FATr (measured in the discrete-sample gas volume,
VS). Since the amount of tracer gas in the lung (alveolar plus dead-space) equals the amount of inspired
tracer gas and given that the dead-space tracer gas fraction is the same as the inspired fraction, we can
generate equations 10 and 11.
VI FITr ¼ VA FATr þ VD FITr (10)
VA ¼ (VI VD ) FITr =FATr (11)
VA is reported under BTPS conditions and then converted to STPD conditions to calculate DLCO, as in
equations 8 and 9. The inspired volume (VI) is the measured volume of inhaled dry gas and is thus
considered to be under ambient temperature (T ), ambient pressure (PB), dry (ATPD) conditions. The
conversion to body temperature, ambient pressure, saturated with water vapour (BTPS) and standard
temperature, pressure, dry (STPD) conditions may require conversion factors to compensate for the
diluting or concentrating effects of adding or removing water vapour or carbon dioxide at the gas
sampling site. Several examples of VA calculations using such conversion factors are given below.
Where water vapour is removed from the sampled gas and carbon dioxide does not interfere with the
analysers we can use equations 12 and 13 as follows, where VABTPS is the alveolar volume under BTPS
conditions and VIATPD is the inspired volume under ATPD conditions.
FITr PB 310
VABTPS ¼ (VIATPD VDequip VDanat ) (12)
FATr (PB 47) (273 þ T)
FITr PB 273
VASTPD ¼ (VIATPD VDequip VDanat ) (13)
FATr 760 (273 þ T)
Where water vapour and carbon dioxide are removed from the sampled gas we can use equations 14 and
15 as follows, where FACO2 is the fraction of carbon dioxide in the alveolar sample. If no measurement of
FACO2 is available then a value of 0.05 may be assumed.
FITr PB 310
FATr (1 FACO2 ) (PB 47) (273 þ T)
FITr PB 273
FATr (1 FACO2 ) 760 (273 þ T)
Where water vapour in the sampled gas is equilibrated to room air, carbon dioxide does not interfere with
the analysers and tank values (i.e. the dry gas concentration) are used for FITr, we can use equations 16
https://doi.org/10.1183/13993003.00016-2016 15
and 17 as shown below. If FITr is read by the analysers, the corrections are the same as in equations 12
and 13 above.
FITr (PB PH2 O ) 310

FATr (PB 47) (273 þ T)
FITr (PB PH2 O ) 273

FATr 760 (273 þ T)
If neither water vapour nor carbon dioxide are removed from the sampled gas, no interference is observed
for the analysers and the sample tubing is heated to prevent condensation, we can use equations 18 and 19
as shown below:
FITr 310
FATr (273 þ T)
FITr (PB 47) 273

FATr 760 (273 þ T)
In all four cases, temperature is measured in degrees Celsius and gas pressures are measured in mmHg. It
is essential that VD is considered in the calculation of VA. VD occurs in two areas: equipment dead-space,
VDequip (i.e. the volume of the mouthpiece, filters and connections within the breathing circuit) and
anatomic dead-space, VDanat (i.e. the volume in the conducting airways that does not participate in gas
exchange). VDequip must be specified by the equipment manufacturer but may vary as the user alters the
system (e.g. by adding a filter or using a different filter). A further small correction to VD can be made
where VDequip is assumed to be under ATPD conditions, since it is filled with room temperature, dry test
gas at the end of inspiration, whereas VDanat should be assumed to be under BTPS conditions. There are
various methods to estimate VDanat. One example uses a fixed value of 150 mL [4, 5], although this does
not work well for small adults or children. Another uses a value of 2.2 mL·kg−1 of body weight [50],
although this does not work well for very obese subjects. In the studies which derive the commonly used
reference equations, the latter is the most commonly used technique. However, some investigators have
ignored VDanat [91–93] and one uses a value derived from age+2.2 mL·kg−1 of body weight [94]. If body
mass index (BMI) is <30 kg·m−2, the recommendation is to use an estimate for VDanat of 2.2 mL·kg−1
body weight. In more obese subjects, or if the weight of the subject is unknown, VDanat (in mL) can be
estimated using equation 20 where height (h) is measured in cm.
VDanat ¼ h2 =189:4 (20)
With classical discrete-sample systems, which collect the alveolar sample in a collection bag or chamber, the
sample-bag residual volume (sometimes called the sample-bag dead-space) dilutes the sample gas and alters
the measured concentrations of the expired gases. The size and direction of the error depends on VS, the
residual volume of the sample bag and its connectors (VSRV) and the gas content of this residual volume. VSRV
could contain test gas, room air, or expired gas from a subject after a DLCO manoeuvre. When VSRV contains
room air, its effect is to reduce the measured concentrations of the expired gases and equation 21 can be used
to adjust for this. Estimates of the potential change in DLCO, in existing systems when no adjustment is made
for sample-bag dead-space, range from 0.3–8% depending on the sample-bag size and VSRV [95].
FATr [adjusted] ¼ FATr [measured] (VS =(VS VSRV )) (21)
For classical systems, manufacturers must report instrument and sample-bag dead-space. Both of these must
be flushed with room air or, if DM and VC are to be calculated, appropriate levels of oxygen before the
single-breath manoeuvre such that they will not contain expiratory gas from a previous subject. VSRV must be
<2% of VS or 10 mL, whichever is larger. Importantly, when RGAs are used to measure the exhaled sample,
there is no residual bag volume to consider (VA is calculated using a mass balance of all inhaled and exhaled
gas; equations 22–26 in the next section).
For normal subjects, the classical single-breath determination of alveolar volume (VAsb) described above
closely matches TLC determined by plethysmography [22, 74]. However, poor gas mixing in patients with
https://doi.org/10.1183/13993003.00016-2016 16
maldistribution of inspired volume (e.g. patients with obstructed airways) can markedly alter tracer gas
dilution leading to values for VAsb that are markedly less than the value of VA determined from the actual
total thoracic gas volume. Observed carbon monoxide uptake is also affected by poor gas mixing under
these conditions and will primarily reflect the carbon monoxide transfer properties of the regions into
which the test gas is distributed. It has been suggested that a separately determined VA value from a more
accurate method (e.g. multiple-breath technique (VAmb) or plethysmography (VAplethys)) could be
substituted for VAsb under these conditions to correct for the effects of maldistribution. However, the
DLCO calculation (equation 7) is based on the volume of gas into which the tracer gas (and carbon
monoxide) distributes, and not the total thoracic gas volume. Moreover, substituting a larger, separately
determined VAmb or VAplethys value assumes that DM and VC properties in the unmeasured lung regions
are similar to those in the measured lung regions, an assumption that is difficult to justify. Additionally, if
VAsb is replaced with a different value, the applicability of the DLCO reference equations is compromised.
Due to these considerations, a separately measured VAmb or VAplethys should not be substituted for VAsb.
Instead, when the value of VAsb is markedly less than that determined separately for VAmb or VAplethys, this
must be reported and the ratio of VAsb to VAmb or VAplethys may optionally be included. For the
subsequent interpretation of DLCO, it should then be noted that the maldistribution of inspired gas
probably contributes to any observed reduction in measured values.
Alveolar volume in RGA systems

As mentioned in the previous section, when an RGA system is used the dead-space volume is measured
rather than estimated. The total dead-space, VD, can be measured from the tracer gas washout curve using the
FOWLER [78] method (figure 6). A linear regression line estimating the slope of phase III of the tracer gas
washout concentration as a function of volume should be calculated using the last half of the expiratory
tracing by volume. The Fowler dead-space is the point where the area between the phase III slope and the
a) 100
Tracer gas concentration
80
% (full scale)
60
Fowler dead-space
40
0 1 2 3 4 5 6
Volume L
b) 100
Tracer gas concentration
80
% (full scale)
60
Fowler dead-space
40
0 1 2 3
Volume L
FIGURE 6 Graphical representation of the calculation of the Fowler dead-space volume in a normal, healthy
subject (a) and a subject with chronic obstructive pulmonary disease (COPD) (b). The single-breath tracer gas
washout is plotted against exhaled lung volume from total lung capacity. The volume at which the shaded area
above the tracer gas washout curve equals the shaded area below the curve is the FOWLER dead-space [78]
which is reported under body temperature, ambient pressure, saturated with water vapour (BTPS) conditions.
https://doi.org/10.1183/13993003.00016-2016 17
tracer gas washout curve equals the area between the peak tracer gas concentration and the tracer gas washout
curve. The anatomic dead-space, VDanat, is equal to the Fowler dead-space minus the equipment dead-space,
VDequip, which includes the filter and/or mouthpiece and which must be supplied by the manufacturer.
The development of RGA systems now allows the analysis of all gas exhaled and provides the opportunity
to enhance the accuracy of VA determinations. Given that the tracer gas can now be monitored throughout
exhalation, there is no need to constrain the measurement of VA to the discrete sample computationally
constructed to determine carbon monoxide uptake. Indeed, using all of the available gas concentration
data has been shown to provide a better estimate of VA [71, 96] than constraining the measurement to a
smaller sample of exhaled gas (as was required by the equipment available in 1957 when the clinical
single-breath method was developed [2]).
This technique uses a mass balance approach to determine VA in which the volume of tracer gas inhaled
and the volume subsequently exhaled are measured and the latter subtracted from the former to determine
the volume of tracer gas remaining in the lung at end-exhalation [71, 96]. The volume of tracer gas left in
the lung is then divided by the end-expiratory tracer gas concentration to give the absolute end-expiratory
lung volume Vee. The TLC is then calculated by adding the expired volume (VE) to Vee and subtracting
VDequip. If VE is the volume expired from the maximum volume during breath-holding (to the end of the
manoeuvre) then the single-breath total lung capacity (TLCsb) can be defined as TLCsb=VE+Vee−VDequip
and VA=TLCsb−VDanat. Residual tracer gas in the lung from a previous manoeuvre can be measured prior
to the start of the current manoeuvre and included in the mass balance equation.
In more detail, VA is calculated using a mass balance equation which states that the tracer gas left in the
lung at end exhalation is equal to all of the tracer gas inhaled minus the tracer gas exhaled. The sum of
the inhaled and exhaled tracer gas volumes is the integral, with respect to time, of flow×tracer gas
concentration where flow is positive for inhalation and negative for exhalation. In this case, Vee (including
VDequip and VDanat) is thus described by equation 22 where t0 is the time at the start of test gas inhalation,
tf is the time at the end of exhalation, Tr(t) is the tracer gas concentration at any time t (adjusted to BTPS
conditions), Tree is the mean tracer gas concentration at end-exhalation and flow(t) is the flow at any time
t (under BTPS conditions).
ð tf
1
Vee ¼ Tr(t) flow(t) dt (22)
Tree t0
Depending upon the signal to noise ratio, the average value of Tr over the last 250 mL can be used for
Tree. Furthermore, when flow(t) is positive during inhalation of dry test gas, it is adjusted by 310/T·PB/
(PB−47) where T is the ambient temperature. All measurements of tracer gas are assumed to be made with
the water vapour pressure in the sample line equilibrated to the water vapour pressure in room air.
The absolute lung volume at any time t, V(t), during the manoeuvre can then be described by equations 23
and 24. The integral of flow(t)dt from time t0 to time tf is the net change in total volume over the entire
manoeuvre and will be zero if the inhaled volume, VI, equals the exhaled volume, VE. The integral of
flow(t)dt from time t0 to time t is the net volume change at any time t. Hence, at the end of the single
breath manoeuvre, V(tf ) is simply equal to Vee-VDequip.
ðt ð tf
V(t) ¼ Vee þ flow(t) dt flow(t) dt VDequip (23)
t0 t0
ð tf
V(t) ¼ Vee flow(t) dt VDequip (24)
t
If the tracer gas has not been completely washed out from a previous DLCO manoeuvre, then the residual
alveolar tracer gas concentration (TrR) measured just prior to the inhalation of test gas must be considered
in the mass-balance equation and Vee is duly described by equation 25.
ð tf
1
Vee ¼ (Tr(t) TrR ) flow(t) dt (25)
(Tree TrR ) t0
https://doi.org/10.1183/13993003.00016-2016 18
The value of VA to be reported in BTPS conditions is described by equation 26. This value is converted to
STPD conditions for use in equation 8 or 9.
VA ¼ VE þ Vee VDanat VDequip (26)
This method has been compared to plethysmography in normal subjects and in patients with lung disease
with various breath-hold times [71, 96]. For normal subjects, there is little difference in DLCO when using
either method to measure VA; however, VA measured by the RGA method is significantly higher than VA
measured by the classical method in subjects with COPD or uncontrolled asthma. The resulting DLCO
measurements in COPD cases are some 8 to 15% higher. Since reference values for DLCO are developed using
normal subjects, existing reference values continue to be applicable using VA measured by the RGA method.
For subjects with COPD the effect of using the RGA VA value will, in isolation, be to calculate an increased
DLCO value. However, the VA measured from a discrete sample will vary with the sample volume and sample
timing [72] such that using the RGA VA value should improve reproducibility of DLCO in these subjects.
Another significant advantage of calculating absolute lung volume at end-exhalation instead of at maximal
inhalation is that the impact of errors due to the assumption of complete gas mixing in the lung is
reduced. For example, in a patient with a TLC of 7 L and a RV of 2 L, a 10% error in TLC (700 mL)
translates into a 10% error in DLCO. However, a 10% error in RV would be 200 mL and when VC is added
to RV the volume error at TLC is only 2.9% which translates into only a 2.9% error in DLCO.
During the transition from classical systems to RGA systems, some laboratories may wish to report DLCO
values using the 2005 ATS/ERS method in combination with those obtained using RGA VA for
comparative purposes. RGA VA values may alter DLCO in some older normal subjects, who have more
heterogeneous distribution of ventilation due to the normal ageing process, and therefore might yield
slightly higher DLCO values compared to current classically derived reference values. As with any set of
reference values, which must be validated in each laboratory, DLCO values using VA must be validated
using a group of normal, healthy subjects. The Global Lung Function Initiative is in the process of
developing all-age predicted values using datasets submitted from 12 countries (www.lungfunction.org).
Inspired gas conditions

In most cases, the test gas inspired from a bag or a compressed gas cylinder with a demand valve is a dry
gas and, as such, is considered to be under ATPD conditions. The inspired volume needs to be converted
into BTPS conditions for use in equations 10 and 11. It is recommended that the VI (BTPS) be reported
and that manufacturers should specify and document inspired gas conditions for each instrument. Since
gas cooling can occur due to decompression through the delivery valve, manufacturers are required to
measure the test gas temperature at the pneumotachometer in a typical system in their testing laboratory
and provide appropriate compensation for gas cooling if necessary.
Carbon dioxide, water vapour and temperature adjustment for alveolar volume calculations
Exhaled gas contains carbon dioxide and water vapour which were not present in the test gas mixture. As
noted previously, some systems remove one or both of these if they interfere with analyser function,
raising both carbon monoxide and tracer gas concentrations. Under these circumstances, adjustments are
required for the increase in FATr used to calculate VA. However, no adjustment for the increase in alveolar
inspired carbon monoxide and tracer gas fractions at time t (FACO,t and FATr,t) is necessary in calculating
the rate of carbon monoxide uptake, since the concentration factor appears in both the numerator and the
denominator of the expression (FATr,t/FACO,t) and the effect therefore cancels itself out. Exhaled gas is
initially at body temperature and some systems allow this to cool, such that the gas volume contracts,
whereas others will provide heat to maintain the temperature. As such, adjustments to BTPS conditions
may be required depending upon the system design. All of these adjustments must be documented by the
manufacturer for their particular system. The conversion factors used to modify calculations in DLCO
manoeuvres are shown in equations 8, 9 and 12–19.
RGA signal alignment

To properly analyse continuous gas samples, the gas concentration signals from the analysers must be
properly aligned with the flow signal from the pneumotachometer (figure 2). The first step is to shift the
concentration signal ahead in time to compensate for the lag time (the time required for the gas to travel
from the aspiration port to the analyser chamber). The lag time is a function of the length and diameter of
the tubing and the analyser aspiration rate. The length of the tubing should be minimised to prevent
mixing of the aspirated sample within the sampling tube, which can blunt the response time through a
process of Taylor dispersion. The amount of mixing will also depend on the configuration of the sampling
https://doi.org/10.1183/13993003.00016-2016 19
circuit, including any valves and junctions, which can create turbulence. It should also be noted that lag
time can vary with gas viscosity and, when helium is used as the tracer gas, this may require dynamic
compensation during exhalation.
An additional shift of each gas concentration signal relative to the flow signal is also required to compensate
for the response time of the analyser. This can be accomplished using an optimal shift equal to the natural
logarithm of twice the time constant of the analyser response [97]. Alternatively, alignment may be achieved
by other signal processing strategies such as cross-correlation techniques (convolution of signals).
For a more accurate DLCO calculation, a third shift equal to the dead-space transit time may be used to
translate the gas concentrations measured at the mouth to the gas concentrations in the alveolar space.
During inhalation, the gas sampled at the aspiration port will not reach the gas-exchanging alveolar space
until at least one dead-space transit time later and, similarly, the gas sampled at the aspiration port during
exhalation is gas that was in the alveolar space one dead-space transit time previously. If a system uses this
further correction the effective breath-hold time in the alveolar space will be reduced (typically by 0.05–
0.15 s) and DLCO will be increased (typically by 0.5–1.5%).
Interpolation between data points may be required to achieve optimal shifting of the gas concentration
data, particularly if lower digitisation rates are used. To reduce errors introduced by interpolation, a
sample rate of 1000 Hz per channel is recommended.
Transfer coefficient of the lung for carbon monoxide

The logarithmic change in carbon monoxide concentration during the breath-hold phase of the
single-breath manoeuver, divided by tBH and the PB of the dry gas is termed KCO. This is equivalent to the
left hand side of equation 5 without the VA term and, conceptually, DLCO is thus equivalent to VA·KCO.
The specific calculations for KCO are shown below as equations 27 and 28; however, if values are required
in SI units, it is necessary to convert 1000 mL(STPD) to mmol as shown in equations 29 and 30.

F ICO F ATr 1 1000 mL 273 PB PH2 O
K CO ¼ ln (27)
F ACO F ITr tBH =60 (PB PH2 O ) 1L 310 760

F ICO F ATr 1
K CO ¼ ln 69:52 (28)
F ACO F ITr tBH

F ICO F ATr 1 1000 mL 273 PB PH2 O 1 mmol
K CO ¼ ln (29)
F ACO F ITr tBH =60 (PB PH2 O ) 1L 310 101:3 22:4 mL

F ICO F ATr 1
K CO ¼ ln 23:29 (30)
F ACO F ITr tBH
It should be noted that the calculation of KCO is completely independent of the gas flow, lung volume and
barometric pressure measured during the manoeuvre. Although the units of the logarithmic change in
carbon monoxide concentration per unit time and per unit pressure are min−1·mmHg−1 (or min−1·kPa−1),
KCO is expressed in units of mL(STPD)·min−1·mmHg−1·L(BTPS) −1 or mmol·min−1·kPa−1·L(BTPS)−1 only
because the basic measurement of the logarithmic change in gas concentration over time is multiplied by
1000 mL(STPD) and then divided by 1 L(BTPS) which changes the magnitude of the value of KCO by
1000 times the BTPS to STPD factor [98].
As VA is not a component of KCO, some users prefer to use KCO as it eliminates the uncertainty in
measurement of VA from the assessment of carbon monoxide uptake. This uncertainty arises from the
assumption that FATr, as measured from the exhaled gas sample, is representative of the entire lung.
However, this same assumption is used to estimate the alveolar carbon monoxide concentration at the
start of breath-holding and KCO measurement is thus subject to the same uncertainty [99].
Mathematically, KCO can be calculated as DLCO/VABTPS. However, KCO should not be reported using the
term DLCO/VA, as it may be inferred from this term that DLCO can be corrected or normalised for VA. In
fact, the relationship between lung volume and carbon monoxide uptake is complex and studies evaluating
the effects of reduced VI (and thus VA) show the relationship to be alinear and certainly less than 1:1
https://doi.org/10.1183/13993003.00016-2016 20
(i.e. the fall in DLCO is far less than the fall in lung volume) [20, 21, 98, 100, 101]. This likely reflects the
fact that alveolar folding–unfolding and capillary volume changes resulting from lung volume changes do
not translate into concomitant and equal changes in DLCO. Thus, while the KCO calculation might add
insight into carbon monoxide uptake properties of the lung [98], it cannot be used as a simple technique
to normalise DLCO for volume.
Optional calculations
Separate equations for inhalation, breath-hold and exhalation
When KROGH [1] developed the measurement of the “diffusion constant” in 1915, she had to design a
manoeuvre that would be compatible with an analytical solution of the equation for gas transfer. She
achieved this by simulating a pure breath-hold manoeuvre and the measurement of DLCO today continues
to be constrained by having the patient perform a rapid inhalation, 10 s of breath-holding and a rapid
exhalation. Deviations from a pure breath-hold manoeuvre cause errors in DLCO because the Krogh
equation is only valid for this case [68, 72].
The gas transfer equation can also be written for inhalation and exhalation, both of which become
equivalent to the breath-holding equation at zero flow. Using data from the continuous monitoring of flow
and the concentrations of carbon monoxide and tracer gas throughout the manoeuvre, an algorithm can
be used to calculate DLCO by numerical methods [53]. This method accounts analytically for the times of
inhalation and exhalation, gives values of DLCO that are not dependent on how rapidly the manoeuvre is
performed and returns a fixed value of DLCO over the entire manoeuvre that accounts for the observed
uptake of carbon monoxide. All of the exhaled gas data can be used to provide a more representative
measurement of DLCO for the whole lung rather than calculating DLCO from a small alveolar gas sample.
Using the “three-equation method” [53] in young, healthy subjects, the standardised manoeuvre gives the
same values for DLCO as the ATS standardised manoeuvre. However, when these same subjects perform
the manoeuvre with slower flows and/or shorter breath-hold times, similar to those seen in patients with
airflow obstruction, the three-equation method gives unchanged DLCO values while the ATS standardised
method yields significantly higher DLCO values [68]. KROGH [1] designed her experiment for normal
subjects and not for patients with lung disease. The standardised manoeuvre penalises lung disease
patients, who cannot perform it adequately; however, with RGA instrumentation it is no longer necessary
to use an arduous, demanding manoeuvre to measure DLCO.
Indices of heterogeneity of ventilation and gas transfer

As noted above, the heterogeneity of ventilation affects DLCO measurement [102, 103]. Gas concentration
data from RGA systems can be used to calculate indices of ventilation nonuniformity, such as the slope of
phase III of the alveolar plateau [90, 104]. However, such indices need to be normalised to account for the
differences in lung volume and the differences in RV/TLC that occur from person to person [79]. Other
measures of mixing efficiency may be calculated from the tracer gas data [53].
Disease processes can also affect the distribution of gas transfer in the lung. Using the three-equation
method, the observed decay in carbon monoxide during exhalation can be compared to the carbon
monoxide decay that would be predicted for a homogeneous lung in which diffusion occurs uniformly. An
index of DLCO heterogeneity has been developed that is capable of distinguishing smokers with normal
lung function and normal DLCO from a control group of nonsmokers [105].
Evaluating the measurement of DLCO

Acceptability, repeatability and quality control
Acceptable manoeuvres are defined in table 3. The volume–time graph should show a smooth, sharp rise
in volume, followed by a stable breath-hold and a smooth, sharp exhalation (figure 3). The gas
concentration graph should show a very sharp rise when test gas is introduced and remain stable until
exhalation followed by an initial rapid decline with a smooth transition to phase III. Variations from this
pattern will indicate leaks. The VI of test gas must be at least 90% of the largest VC measured in the same
pulmonary function testing session. At least 85% of test gas VI must be inhaled within <4 s. There must be
no evidence of a Müller or Valsalva manoeuvre during the breath-hold period. Alveolar sample collection
must be completed within 4 s. The calculated breath-hold time must be 10±2 s. For RGA systems, virtual
sample collection should be initiated after the completion of dead-space washout. A manoeuvre with a
VI/VC <90% but ⩾85% may be deemed acceptable if the VA is within 200 mL or 5% (whichever is greater)
of the largest VA from other acceptable manoeuvres.
Repeatability describes intra-session variability on repeated testing when there is no change in test
conditions [106, 107]. In a large university-based laboratory study, the coefficient of variation for repeated
measurement in normal subjects was 3.1% and this increased only slightly (from 4.0 to 4.4%) in patients
https://doi.org/10.1183/13993003.00016-2016 21
TABLE 3 Acceptability, repeatability and quality control in DLCO testing
Criteria for acceptability
A VI ⩾90% of the largest VC in the same test session; alternatively a VI ⩾85% of the largest VC in the
same test session and VA within 200 mL or 5% (whichever is greater) of the largest VA from other
acceptable manoeuvres
85% of test gas VI inhaled in <4 s
A stable calculated breath-hold for 10±2 s with no evidence of leaks or Valsalva/Müller manoeuvres
during this time
Sample collection completed within 4 s of the start of exhalation. For RGA systems, virtual sample
collection should be initiated after dead-space washout is complete
Criteria for repeatability
At least two acceptable DLCO measurements within 2 mL·min−1·mmHg−1 (0.67 mmol·min−1·kPa−1)

of each other
Quality control grading#

Score V I/VC t BH Sample collection
A ⩾90%¶ 8–12 s ⩽4 s
B ⩾85% 8–12 s ⩽4 s
C ⩾80% 8–12 s ⩽5 s
D ⩽80% <8 or >12 s ⩽5 s
F ⩽80% <8 or >12 s >5 s
VI: inspired volume; VC: vital capacity; VA: alveolar volume; tBH: breath-hold time; DLCO: diffusing capacity of
the lung for carbon monoxide. #: only grade A manoeuvres meet all acceptability criteria. The average DLCO
values from two or more grade A manoeuvres that meet the repeatability criterion should be reported. If
only one grade A manoeuvre is attained, the DLCO value from that manoeuvre should be reported. If no
grade A manoeuvre is obtained, manoeuvres of grades B to D might still have clinical utility. The average of
such manoeuvres should be reported but these deviations from the acceptability criteria must be noted to
caution the interpreter of the test results. Manoeuvres of grade F are not useable. ¶: or VI/VC⩾85% and VA
within 200 mL or 5% (whichever is greater) of the largest VA from another acceptable manoeuvre.
with abnormal spirometry patterns [108]. Studies conducted prior to the publication of the 2005 standards
found DLCO variability of up to 9% (reproducibility) in normal individuals in repeated measurement over a
period of 1 year [109] and coefficients of variation ranged from 6.2% to 12% in selected UK regions [110].
Repeatability requirement: there must be at least two acceptable manoeuvres that are within
2 mL·min−1·mmHg−1 (0.67 mmol·min−1·kPa−1) of each other. A study of 4797 test sessions found that 95.5%
of cases met this criterion [67]. Since most intra-session variability is technical rather than physiological, the
mean of acceptable manoeuvres is reported. The average of at least two acceptable manoeuvres that meet the
repeatability requirement must be reported (i.e. outliers excluded). While it is recommended that at least two
acceptable DLCO manoeuvres must be performed, research is needed to determine the actual number of
manoeuvres required to provide a reasonable estimate of average DLCO for a given person. As noted elsewhere,
five manoeuvres will result in an increase of ∼3.5% COHb from baseline [66, 82], which will decrease the
measured DLCO by ∼3–3.5%. Thus, conducting more than five manoeuvres is not a recommended strategy.
There are no quality control grading systems that have been validated using the new standards contained
in this document. Until such validation is published, an interim grading system is provided in table 3 and
further research is recommended to develop and validate a DLCO grading system.
A grade A manoeuvre meets all acceptability criteria. The average DLCO from two or more grade A
manoeuvres that are repeatable (i.e. are within 2 mL·min−1·mmHg−1 or 0.67 mmol·min−1·kPa−1 of each
other) should be reported. If, after repeat testing, the operator is unable to obtain two repeatable grade A
manoeuvres, then the following values are reported with a caution to the interpreter that the testing
session was suboptimal: 1) If two or more grade A manoeuvres that are not repeatable are obtained, then
the average DLCO value from the acceptable manoeuvres is reported. 2) If only one grade A manoeuvre is
obtained, then the DLCO value from that manoeuvre is reported. 3) If no acceptable manoeuvres are
obtained, then the average DLCO value of the manoeuvres with grades B, C or D is reported. 4) If only
grade F manoeuvres are obtained, then no DLCO value is reported.
https://doi.org/10.1183/13993003.00016-2016 22
Adjustments to the predicted value of DLCO prior to interpretation

The value of DLCO depends upon a number of physiological factors. Besides varying with age, sex, height
and possibly ethnicity, DLCO also changes with Hb, lung volume, COHb, PIO2 (inspired oxygen tension,
e.g. altitude), exercise and body position. Although these effects may cause changes in DLCO in opposite
directions [111], all should be considered in interpreting the observed carbon monoxide uptake. It is
recommended that adjustments for these factors be made in the predicted rather than the measured DLCO
value. The predicted DLCO value is derived from measurements in normal subjects who are disease free,
have normal Hb levels and minimal COHb, are sitting at rest, and breathing room air. If any of these
conditions are not met, then the predicted value should be adjusted accordingly.
Adjustment for haemoglobin

Since carbon monoxide–Hb binding is such an important factor in carbon monoxide transfer, DLCO
changes can be substantial as a function of Hb concentration [111–115]. The empirical effect upon DLCO
with change in Hb closely matches what is expected from a theoretical approach using the relationship in
equation 3, with θ assumed to be proportional to Hb, DM/θVC assumed to be 0.7 [113] and the “standard”
Hb value assumed to be 14.6 g·dL−1 (9 mmol·L−1) in adult and adolescent males and 13.4 g·dL−1
(8.26 mmol·L−1) in adult females and children <15 years old. Using these relationships and expressing Hb
in g·dL−1, the predicted DLCO in adolescents and adult males can be adjusted using equation 31, while that
in children <15 years of age and females is adjusted using equation 32. Results from a more recent study
in patients with a wide range of Hb abnormalities [115] show a slightly greater and more linear
relationship; however, corrected values are generally consistent with equations 31 and 32.
DLCO [predicted for Hb] ¼ DLCO [predicted] (1:7Hb=(10:22 þ Hb)) (31)
DLCO [predicted for Hb] ¼ DLCO [predicted] (1:7Hb=(9:38 þ Hb)) (32)
The measurement of Hb in the American population [116] found deviation from these standard values,
especial in males, children and seniors; differences were also found between Caucasian and
African-Americans. Furthermore, the survey found that Hb levels in the general population are changing
over time. If a more appropriate reference Hb level (Hbref ) is available then the predicted DLCO is adjusted
using equation 33.
DLCO [predicted for Hb] ¼ DLCO [predicted] (1:7Hb=(0:7Hbref þ Hb)) (33)
Adjustments for alveolar oxygen tension

As noted previously, PAO2 affects the measurement of DLCO and changes to PAO2 (such as supplemental
oxygen breathing that gives higher PAO2 values) will have a correlating effect on DLCO values. The value of
DLCO will change by ∼0.35% for each 1 mmHg change in PAO2 or ∼2.6% for each 1 kPa change in PAO2 [117,
118]. Adjustments to the predicted DLCO in a subject on supplemental oxygen may be made using a
measured PAO2, where PAO2=FIO2·(PB−47) and assuming a normal PAO2 in room air at a sea level of 100
mmHg (13.3 kPa). This is shown in equation 34 below or equation 35 if SI units are preferred.
DLCO [predicted for elevated PAO2 ] DLCO [predicted]=(1:0 þ 0:0035(PAO2 100)) (34)
TLCO [predicted adjusted for PAO2 ] TLCO [predicted]=(1:0 þ 0:026(PAO2 13:3)) (35)
Some pulmonary function systems include measurement of carbon dioxide. In these systems, the
end-expiratory carbon dioxide concentration can be used to estimate the alveolar oxygen partial pressure
using the simplified alveolar gas equation. In patients who have higher carbon dioxide levels (higher PACO2)
and consequently lower PAO2 values, the predicted DLCO can be corrected to compensate for the increase in
DLCO that arises. For example, at a barometric pressure of 760 mmHg (101.3 kPa), if the PACO2 in a patient
retaining carbon dioxide was 50 mmHg (6.67 kPa) then the PAO2 would be 86 mmHg (11.5 kPa) and the
predicted DLCO would be 4.8% higher than if the PACO2 were 40 mmHg (5.33 kPa). However, there are many
assumptions inherent in this approach and more research is needed to determine the validity of such an
adjustment.
https://doi.org/10.1183/13993003.00016-2016 23
Adjustment for carboxyhaemoglobin concentration and carbon monoxide back-pressure

As noted previously, COHb can affect the measured uptake of carbon monoxide in the following two ways
[119–121]. First, by occupying Hb binding sites, carbon monoxide produces an “anaemia effect”. Secondly,
carbon monoxide partial pressure in the blood will reduce the driving pressure for carbon monoxide
transport from alveolar gas to capillary blood. Exposure to ordinary environmental carbon monoxide and
endogenous production of carbon monoxide as a byproduct of Hb catabolism commonly results in
measured COHb levels of 1–2% [119]. However, cigarette smoke and other environmental sources can
produce measurable levels of carbon monoxide back-pressure and COHb that may need to be considered
in the measurement of carbon monoxide uptake [119].
The inhalation of carbon monoxide in the single-breath manoeuvre causes COHb to increase by 0.6–0.7%
for each manoeuvre [66, 82]. The adjustment of the predicted DLCO value for carbon monoxide was found
to be −0.938% per 1.0% increase in COHb [122]. For RGA systems, carbon monoxide back-pressure can
be measured in expired gas prior to the inspiration of test gas in the DLCO manoeuvre [62] and can be
compensated for analytically. For classical systems, carbon monoxide back-pressure can be estimated using
one of several available techniques [121, 123–125]. For example, carbon monoxide back-pressure can be
calculated from COHb using equation 36, where COHb and O2Hb are the fractions of carbon monoxide
and oxygen-bound haemoglobin, respectively.
FACO ¼ (COHb=O2 Hb) (FAO2 )=210 (36)
DLCO can then be recalculated after subtracting the estimated carbon monoxide back-pressure from both
the initial and final alveolar carbon monoxide partial pressures (units must be consistent before making
the subtraction). Unfortunately, this method will not adjust DLCO for the “anaemia effect” of COHb;
however, several studies have evaluated both the empirical and theoretical effects of COHb on DLCO and
incorporated both the back-pressure and the “anaemia effect” of COHb into the adjustment. In general, a
1% increase in COHb reduces the measured DLCO by ∼0.8–1% from both effects [16, 17]. Using this
approach, equation 37 empirically reduces predicted DLCO by 1% for each percentage point of COHb >2%.
DLCO [predicted for COHb] ¼ DLCO [predicted] (102% COHb%) (37)
A more recent study using an RGA system to measure alveolar carbon monoxide concentration, combined
with venous measurement of COHb, found that the effect of carbon monoxide back-pressure and the
“anaemia effect” are almost equal and the combined effect is a 2% decrease in DLCO for each 1% increase
in COHb [62]. These findings were verified in a discrete sample system [66]. In these studies, where the
carbon monoxide back-pressure was measured and used in the calculation of DLCO, equation 38 was used
to further correct for the “anaemia effect” where FACOb is the alveolar carbon monoxide fraction in ppm
measured at the end of exhalation to residual volume, just prior to the inhalation of test gas.
DLCO [corrected] ¼ DLCO (1 þ FACOb =560) (38)
As endogenous COHb (1–2%) was present in the healthy nonsmoking subjects from whom prediction
equations were generated, an adjustment for COHb is only recommended for interpretative purposes when
COHb levels are known to be elevated or levels above 2% are suspected. Methaemoglobin (MetHb) will
not bind carbon monoxide meaning there is, effectively, a reduced amount of haemoglobin available and
leading to a similar “anaemia effect”. Since there is effectively less Hb to bind with carbon monoxide
during the DLCO manoeuvre, the measured DLCO is reduced. An adjustment for MetHb has been proposed
[126] and is shown in equation 39.
Hb[adjusted] ¼ Hb (100 MetHb=100) (39)
Adjustment of DLCO for barometric pressure

For factors such as Hb that are related to the individual subject, the recommended adjustment is made to
the predicted DLCO value. However, barometric pressure (PB) is an environmental factor that is
https://doi.org/10.1183/13993003.00016-2016 24
independent of the individual and therefore the adjustment should be made to the measured DLCO value
to simulate standard pressure conditions. The variation in DLCO due to the typical range in high and low
pressure cells at a given altitude is approximately ±1.5%. PB decreases with altitude (such that PIO2
decreases) and DLCO increases by about 0.53% for each 100 m of increase in altitude. Moreover, the
applicability of using a reference value data set from a different location is improved if both the measured
DLCO and the predicted value of DLCO are adjusted to standard pressure (760 mmHg or 101.3 kPa). The
adjustment for PB [4, 117] assumes a PIO2 of 150 mmHg (20 kPa) at standard pressure and can be
calculated using equations 40 (PB in mmHg) and 41 (PB in kPa).
DLCO [PB adjusted] DLCO (0:505 þ 0:00065 PB ) (40)
DLCO [PB adjusted] DLCO (0:505 þ 0:00488 PB ) (41)
For DLCO reference values that do not provide PB data, the altitude of the centre in which the reference
values were obtained can be used to estimate PB [127] using equations 42 and 43 where a is the altitude
above sea level in metres. It should be noted that the relationship between DLCO and PB has not been
confirmed using an RGA system. Further research is needed to validate the use of equations 40 and 41.
PB [mmHg] ¼ 760 (1 2:25577 105 a)5:25588 (42)
PB [kPa] ¼ 101:325 (1 2:25577 105 a)5:25588 (43)
Reporting values
This document is intended to establish technical standards which, in terms of reporting, will require DLCO
systems to be able to report the variables listed in table 4. It is not intended to specify which variables end
users should include in the report forms used in their laboratories, nor is it intended to address the
interpretation of DLCO. Although work is ongoing towards establishing a standardised pulmonary function
laboratory report form, there is no current standard. A DLCO system must be able to report the unadjusted
measured DLCO, the DLCO adjusted for PB, the lower limit of normal and z-score, predicted, and
percentage of predicted DLCO, KCO, the lower limit of normal and z-score, predicted, and percentage of
predicted KCO. Any adjustments (e.g. for Hb, COHb, PIO2 or lung volume) must also be reported along
with the data used to make them. The average VA must be reported along with the predicted VA (the
predicted TLC minus the predicted VD) and percentage of predicted VA. If available, a separately measured
TLC and VA/TLC ratio may be reported, although this is optional. The average VI must also be noted. If a
separately measured VC is available, it must be reported to serve as a reference for the adequacy of VI. In
addition, comments relevant to the quality of the measurements recorded must be included. A complete
list of specifications for which variables and measurements that DLCO systems are able to report is given
in table 4. While the use of z-scores is favoured in the interpretation of pulmonary function results, given
the continuing use of “percentage of predicted” values in many laboratories, the ability to report both
z-scores and percentage of predicted values is recommended.
Specifications for reports and output of results

Although standardised reporting forms are being considered, manufacturers have diverse options for
reporting of results. This is due, in a large measure, to the insistence of various pulmonary function
laboratories on having a customised report that matches their historic format. A common option for
accommodating electronic medical records, is the provision of a pdf document; however, a universal
format for data output in the form of a csv or xml formatted data file has been proposed. This format
should include the results and demographic/environmental data for each test in a format that will permit
the user to import data to and their own reporting formand export to their particular electronic record.
The data file must include all data necessary to calculate the variables listed in table 4. For RGA systems,
the data arrays for flow, carbon monoxide and tracer gas must be included and must be adjusted for
auto-zero and calibration factors, with the optimal shift applied to the concentration data. Flow data must
be converted to BTPS conditions and the data must include the equipment dead-space, the washout
volume, the alveolar sample volume, the barometric pressure and the carbon monoxide and tracer gas
concentrations at end-exhalation prior to the inhalation of test gas. Manufacturers must provide the
format details to permit users to import the data. The complete specifications for the data file are given in
the supplementary materials.
https://doi.org/10.1183/13993003.00016-2016 25
TABLE 4 DLCO reporting requirements
Variable# Requirement
DLCO (unadjusted) Required

DLCO (adjusted for PB) Required
DLCO (LLN and/or z-score) Required
DLCO (predicted) Required
DLCO (adjusted,predicted) Optional (required if any adjustments
made-specify adjustments)
DLCO (% of predicted) Required
VA (BTPS) Required
VA (LLN and/or z-score) Required
VA (% of predicted) Optional
KCO Required
KCO (LLN and/or z-score) Required
KCO (predicted) Required
KCO (% of predicted) Required
PB Required
tBH Required
VI (BTPS) Required
Fowler (anatomic) dead-space Required for RGA systems
TLCsb Required for RGA systems
Reference values source Required
Test quality grade Recommended (include % variability in
DLCO acceptable manoeuvres)
Operator comments Required (number of manoeuvres, number
of acceptable manoeuvres)
Graphs Required (full manoeuvre and exhaled
gas concentration versus volume with sample
collection indicated for RGA systems)
Hb Optional (required if used to adjust DLCO)
COHb Optional (required if used to adjust DLCO)
Alternative calculations (e.g. three-equation DLCO, Optional
normalised slope of phase III)
BTPS: body temperature, ambient pressure, saturated with water vapour; LLN: lower limit of normal; DLCO:
diffusing capacity of the lung for carbon monoxide; VA: alveolar volume; KCO: transfer coefficient of the lung
for carbon monoxide; PB: barometric pressure; tBH: breath-hold time; VI (BTPS): inspired volume under BTPS
conditions; VA (BTPS): alveolar volume under BTPS conditions; TLCsb: single-breath total lung capacity;
Hb: haemoglobin; COHb: carboxyhaemoglobin; RGA: rapidly responding gas analyser. #: for DLCO, VA, KCO,
tBH, VI, VDanat and TLCsb the average values from the acceptable and repeatable manoeuvres are reported.
Reference values
The Global Lung Health Initiative (GLI) is currently working on the development of global reference
values for DLCO which will very likely be in a similar structure to the GLI spirometry reference values
[128]. Implementation of these reference values requires more complexity than simply inserting
coefficients for polynomials and a DLCO system must be able to implement this method of calculating
reference values. A list of reference values for DLCO developed using methods that adhere to the 2005
DLCO standards is provided in table 5 [4].
Summary
It is not the intention of the new standards to render older equipment or instrumentation with alveolar
sample chambers or bags, that is still in current use, obsolete. The 2005 ATS/ERS standards address this
type of instrumentation. It is recognised that some equipment which meets the 2005 standards will
continue to be used but the expectation is that new equipment will meet or exceed the new standards.
Some of the systems currently available will be able to meet the new standards with software upgrades.
As already noted, the changes in DLCO standards will not impact the applicability of reference values. In
general, pulmonary function measurements are more accurate and precise in normal, healthy subjects than
in patients with lung disease so that changes which improve the measurement of DLCO will have less
impact on normal, healthy subjects, which favours the continued applicability of reference values derived
using older systems. There are already systematic differences among reference value sets for DLCO which
are related to the equipment and methodology which impact their applicability. Some reference values
https://doi.org/10.1183/13993003.00016-2016 26
TABLE 5 Reference values for DLCO from studies that complied with the 2005 American
Thoracic Society/European Respiratory Society DLCO standards
Author# Year Country Age Subjects
Thompson [129] 2008 Australia 45–71 years 498 male/474 female

Koopman¶ [130] 2011 Netherlands 7–18 years 278 male/265 female
Garcia-Rio¶ [131] 2012 Spain 65–85 years 169 male/262 female
Kim [132] 2012 USA and Australia 5–19 years 225 male/254 female
Thomas [133] 2014 Denmark 5–17 years male/female (297 total)
Michailopoulos [134] 2015 Greece 18–91 years 234 male/233 female
Verbanck [135] 2016 Belgium 20–80 years 128 male/124 female
DLCO: diffusing capacity of the lung for carbon monoxide. #: only studies with at least 100 males and 100
females are included. All of these reference values were derived using caucasian subjects. ¶: test gas
contained 19% oxygen (all other studies used test gas with 21% oxygen).
currently in use were developed prior to the publication of the 2005 ATS/ERS standards [4]. Hence, there
is already a pressing need for reliable, comprehensive reference values for DLCO.
Advances in technology have outpaced guidelines and standards. These revisions to the DLCO standards
are required to make optimal use of existing, clinically available technology. Guidelines and standards
should not constrain progress in the improvement of pulmonary function measurements but should serve
to continually improve the quality of DLCO measurements.
Recommendations for research directions

In the course of developing these technical standards, the following areas were identified as candidates for
research studies to fill knowledge gaps and provide more specific guidelines.
1) Conduct studies of DLCO in normal, healthy subjects in ethnicities other than Caucasian over a wide
age range to either validate the use of Caucasian reference values or develop ethnicity-specific
reference values.
2) Develop a standardised common report form for pulmonary function testing that can be the default
for all laboratories and electronic medical record systems.
3) Determine the effect of barometric pressure on DLCO in normal subjects and COPD patients over a
range of pressures reflecting altitudes from sea level to 2500 m to either confirm or replace equations
40 and 41.
4) Determine the effects of obesity on VDanat, TLCsb and DLCO.
5) Determine whether Hb measured by skin prick or venipuncture is more appropriate for DLCO
adjustment and conduct studies to confirm or revise the relationship between Hb and DLCO
expressed in equations 31 and 32.
6) Determine normal Hb levels in populations of different ethnicity and geographical location.
7) Test the proposed DLCO grading scale in large clinical databases for both classical and RGA DLCO
systems.
8) Determine the impact of carbon dioxide retention on DLCO measurements.
9) Determine the sensitivity and action levels for the assessment of gas analyser linearity using the
dilution of test gas in a calibration syringe.
10) Determine the repeatability of calculating VA and TLCsb by the method in equation 26 which uses
all of the tracer gas concentration data throughout the manoeuvre.
In addition to these research directions, there is also a need to update the guidelines for the interpretation
of pulmonary function tests in general and of DLCO in particular.
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TASK FORCE REPORT

ERS/ATS TECHNICAL STANDARDS

2017 ERS/ATS standards for single-breath

This article has supplementary material available from erj.ersjournals.com

https://doi.org/10.1183/13993003.00016-2016 Eur Respir J 2017; 49: 1600016

Determinants of carbon monoxide uptake

VA DFACO =Dt ¼ PACO DLCO (1)

DLCO ¼ VA DFACO =Dt=PACO (2)

1=DLCO ¼ 1=DM þ 1=uVC (3)

Gas analysers and general equipment

Flow and volume analysers

RGA response time

TABLE 1 Equipment specifications and performance standards

DLCO System Specification

Rapid gas analyser systems

Classical discrete sample systems

Concentration % (full scale)

Linearity and accuracy

Interference and noise

Other equipment considerations

Equipment calibration and quality control

TABLE 2 Equipment calibration schedule

Calibration technique Frequency

Flow analyser zeroing Before each test

DLCO: diffusing capacity of the lung for carbon monoxide.

Quality control for RGA systems

Standardisation issues in the single-breath testing technique

Breath-hold and expiratory manoeuvres

Washout and sample collection manoeuvres

Washout and sample collection in classical systems

Washout and sample collection in RGA systems

Concentration % (full scale)

Tracer gas Tracer gas

Concentration % (full scale)

Tracer gas Tracer gas

Inspired gas composition

Manoeuvre intervals in RGA systems

Pulmonary function test sequence

If we convert VA to STPD conditions we obtain equation 8 for traditional units of DLCO

Calculating breath-hold time

Inhalation Breath-holding Exhalation

Calculating the alveolar volume

VI FITr ¼ VA FATr þ VD FITr (10)

VA ¼ (VI VD ) FITr =FATr (11)

FITr (PB PH2 O ) 310

FITr (PB PH2 O ) 273

FITr (PB 47) 273

VDanat ¼ h2 =189:4 (20)

FATr [adjusted] ¼ FATr [measured] (VS =(VS VSRV )) (21)

Alveolar volume in RGA systems

VA ¼ VE þ Vee VDanat VDequip (26)

Inspired gas conditions

RGA signal alignment

Transfer coefficient of the lung for carbon monoxide

Indices of heterogeneity of ventilation and gas transfer

Evaluating the measurement of DLCO

TABLE 3 Acceptability, repeatability and quality control in DLCO testing

Criteria for acceptability

Criteria for repeatability

At least two acceptable DLCO measurements within 2 mL·min−1·mmHg−1 (0.67 mmol·min−1·kPa−1)

Quality control grading#

Adjustments to the predicted value of DLCO prior to interpretation

Adjustment for haemoglobin